Obesity is associated with a reduction in life expectancy and an increase in mortality
from cardiovascular diseases, cancer, and other causes. We therefore assessed the
efficacy and safety of two doses of phentermine plus topiramate controlled-release
combination as an adjunct to diet and lifestyle modification for weight loss and metabolic
risk reduction in individuals who were overweight and obese, with two or more risk
factors.
In this 56-week phase 3 trial, we randomly assigned overweight or obese adults (aged
18-70 years), with a body-mass index of 27-45 kg/m(2) and two or more comorbidities
(hypertension, dyslipidaemia, diabetes or prediabetes, or abdominal obesity) to placebo,
once-daily phentermine 7·5 mg plus topiramate 46·0 mg, or once-daily phentermine 15·0
mg plus topiramate 92·0 mg in a 2:1:2 ratio in 93 centres in the USA. Drugs were administered
orally. Patients were randomly assigned by use of a computer-generated algorithm that
was implemented through an interactive voice response system, and were stratified
by sex and diabetic status. Investigators, patients, and study sponsors were masked
to treatment. Primary endpoints were the percentage change in bodyweight and the proportion
of patients achieving at least 5% weight loss. Analysis was by intention to treat.
This study is registered with Clinical Trials.gov, number NCT00553787.
Of 2487 patients, 994 were assigned to placebo, 498 to phentermine 7·5 mg plus topiramate
46·0 mg, and 995 to phentermine 15·0 mg plus topiramate 92·0 mg; 979, 488, and 981
patients, respectively, were analysed. At 56 weeks, change in bodyweight was -1·4
kg (least-squares mean -1·2%, 95% CI -1·8 to -0·7), -8·1 kg (-7·8%, -8·5 to -7·1;
p<0·0001), and -10·2 kg (-9·8%, -10·4 to -9·3; p<0·0001) in the patients assigned
to placebo, phentermine 7·5 mg plus topiramate 46·0 mg, and phentermine 15·0 mg plus
topiramate 92·0 mg, respectively. 204 (21%) patients achieved at least 5% weight loss
with placebo, 303 (62%; odds ratio 6·3, 95% CI 4·9 to 8·0; p<0·0001) with phentermine
7·5 mg plus topiramate 46·0 mg, and 687 (70%; 9·0, 7·3 to 11·1; p<0·0001) with phentermine
15·0 mg plus topiramate 92·0 mg; for ≥10% weight loss, the corresponding numbers were
72 (7%), 182 (37%; 7·6, 5·6 to 10·2; p<0·0001), and 467 (48%; 11·7, 8·9 to 15·4; p<0·0001).
The most common adverse events were dry mouth (24 [2%], 67 [13%], and 207 [21%] in
the groups assigned to placebo, phentermine 7·5 mg plus topiramate 46·0 mg, and phentermine
15·0 mg plus topiramate 92·0 mg, respectively), paraesthesia (20 [2%], 68 [14%], and
204 [21%], respectively), constipation (59 [6%], 75 [15%], and 173 [17%], respectively),
insomnia (47 [5%], 29 [6%], and 102 [10%], respectively), dizziness (31 [3%], 36 [7%],
99 [10%], respectively), and dysgeusia (11 [1%], 37 [7%], and 103 [10%], respectively).
38 (4%) patients assigned to placebo, 19 (4%) to phentermine 7·5 mg plus topiramate
46·0 mg, and 73 (7%) to phentermine 15·0 mg plus topiramate 92·0 mg had depression-related
adverse events; and 28 (3%), 24 (5%), and 77 (8%), respectively, had anxiety-related
adverse events.
The combination of phentermine and topiramate, with office-based lifestyle interventions,
might be a valuable treatment for obesity that can be provided by family doctors.
Vivus.
Copyright © 2011 Elsevier Ltd. All rights reserved.